S302: COST-EFFECTIVENESS OF KTE-X19 IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA
Authors: M. Marchetti, C. Visco
Journal: HemaSphere (2022)

Background: Relapsed/refractory (R/R) mantle-cell lymphoma (MCL) post BTK-i has a poor prognosis when treated with currently available treatments with median overall survival between 6 to 15 months. In the ZUMA-2 study, KTE-X19, a chimeric antigen receptor (CAR) T-cell therapy, displayed very high response rate (93% overall objective response rate) with 83% of patients in the study alive at 12 months (Wang et al 2020). An indirect comparison of overall survival from ZUMA-2 with patients receiving standard of care (SOC) treatment reported propensity-adjusted HR 0.32-0.49 (Hess et al 2021). Based on such data, international scientific societies (NCCN, ESMO) recommend the use of CAR-T for R/R MCL patients and marketing authorization of KTE-X19 was granted by FDA and EMA. Aims: The present study aimed to estimate the long-term clinical benefits and overall healthcare costs of KTE-X19 in R/R MCL patients post BTK-i from the perspective of the Italian HealthCare System, compared to current standard therapy for these patients in Italy: rituximab-bendamustine-cytarabine (R-BAC). Methods: A partitioned-survival model was used to extrapolate overall survival, progression-free survival, quality-adjusted survival and healthcare costs of R/R MCL patients over a lifetime horizon, assuming that patients who had not relapsed within 5 years experienced long-term remission. R-BAC (6 cycles) was used as baseline SOC, however a mix of treatments was tested as sensitivity analysis. The source of safety and survival data for KTE-X19 was the ZUMA-2 trial (median potential follow up 28.8 mo), while data from retrospective real-world studies, including SCHOLAR-2, were used for SOC. The healthcare costs for patients assigned to the CAR-T strategy included bridging chemotherapy (36.8% of the patients), hospitalization (median length 21.2 days, of which 23% in intensive care), and the price of KTE-X19. The healthcare costs of patients assigned to SOC included in addition to R-BAC treatment costs, the cost for allogeneic hematopoietic stem cell transplant (€179,418) for 31% of patients (McCullogh 2020). Life years (LYs), quality-adjusted life years (QALYs) and costs were estimated by discounting future outcomes (3% per year). Uncertainty analysis included one-way and probabilistic sensitivity Results: Over a lifetime horizon, mean estimated survival was 8.85 years for KTE-X19 and 1.56 years for R-BAC, while discounted QALYs were 6.40 for KTE-X19 versus 1.20 for R-BAC. Discounted lifetime costs were €411,403 for KTE-X19 versus €74,415 for R-BAC, which corresponds to a cost of €64,798 per QALY gained and €46,264 per LY gained. Detailed results are reported in the table below. The ICERs for KTE-X19 versus SCHOLAR-2 based and meta-analysis based comparisons were €57,915, and €56,010, respectively. The most influential model parameters were patients age and quality of life values, KTE-X19 acquisition cost, and the proportion of patients receiving allo-SCT in the comparator arm, and model time horizon. Probabilistic sensitivity analysis showed that at a willingness-to-pay of €70,000 per QALY, the probability of KTE-X19 to be cost-effective was 65%. Image:Summary/Conclusion: This analysis shows that KTE-X19 may be a cost-effective alternative to R-BAC for patients with RR-MCL pre-exposed to BTK-i and chemoimmunotherapy, from an Italian third-party payer perspective